Effect of R-(-)-α-methylhistamine and thioperamide on in vivo release of norepinephrine in the rat hippocampus

1. The modifications of hippocampal release of norepinephrine following the administration of R-(-)-α-methylhistamine and thioperamide, respectively agonist and antagonist of histamine H₃ receptors, were assessed in freely moving rats by microdialysis. 2. Both the systemic (2 mg/kg i.p.) and local (100 μM via the probe) administration of thioperamide caused no modifications of basal release, indicating that the histaminergic system is not tonically involved in regulating the hippocampal noradrenergic activity. 3. R-(-)-α-methylhistamine (1 and 100 μM) produced a slight, short-lasting and dose-dependent reduction of norepinephrine release antagonized by local perfusion (100 μM) and prevented by systemic administration of thioperamide 2 mg/kg. 4. The results seem to indicate that the modulation of norepinephrine release through presynaptic H3-receptors in the rat hippocampus plays a minor role in the memory-enhancing effects of thioperamide.